We propose what we believe to be a novel metastructure consisting of silicon nanoblock tetramer clusters and investigated theoretically and experimentally how to enhance surface sensing capabilities with polarization-independent properties through bound states in the continuum (BICs). By introducing square defects, three quasi-BIC modes are excited at the wavelengths of 1013.29 nm, 1109.57 nm, and 1310.73 nm with a modulation depth up to 100% and a Q-factor of 16618, while achieving a sensitivity of 256 nm/RIU and a figure of merit of 2519.7 RIU−1. Utilizing the finite-difference method in the time domain (FDTD), we have analyzed the electromagnetic near-field distributions, polarization properties, and robustness corresponding to resonance dips at different wavelengths. Our results reveal that the distinct electromagnetic near-field distributions excited by the quasi-BIC modes are characterized by the strong field confinement within the silica nanoblock tetramer clusters. The modes are primarily governed by magnetic quadrupole (MQ) resonance and toroidal dipole (TD) moment. Additionally, the polarization-independent properties of the metastructure are demonstrated to ensure that they can effectively respond to the incident light regardless of its polarization state, while the robustness is investigated to show the stability and reliability by shifting square defects. Moreover, the transmission spectra of the metastructure is experimentally verified by immersing the sample into CaCl2 solutions in different concentrations. This work plays a pivotal role in creating further novel and high-performance optical metastructures while demonstrating the potential applications of quasi-BIC modes in precision sensing in the future.